Contribution of the Regulatory Gene lasR to the pathogenesis of Pseudomonas aeruginosa infection of burned mice

Pseudomonas aeruginosa is a gram-negative opportunistic pathogen that cause s severe infections in patients with burns. The P aeruginosa regulatory gen e, lasR, regulates the expression of several virulence factors. The specifi c lasR isogenic mutant, PAC-R1, is defective in the synthesis of the 2 elas tases (LasB and LasA) and produces low levels of exotoxin A. and alkaline p roteases. In this study, we used a burned mouse model to examine the role o f lasR in the pathogenesis of P aeruginosa infections. We have examined the following aspects of P aeruginosa infections: 1) lethality to the burned m ouse, 2) the dissemination within the body of the burned mouse, and 3) the local spread within the burned skin. In comparison with its parent strain, PAO1, PAC-R1 was less lethal. In addition, the numbers of PAO-R1 microorgan isms recovered from the livers and spleens of the burned mice were less tha n those of PAO1. Furthermore, at 8 hours postinfection, equivalent numbers of PAO1 and PAO-R1 were detected at the inoculation site of the burned skin . However, only PAO1 microorganisms were detected at other sites of the bur ned skin. These results suggest that the lasR gene contributes (directly an d indirectly) to the dissemination of P aeruginosa within the body of burne d mice and its horizontal spread within the burned skin.